scholarly journals Innate immunity pathways activate cell proliferation after penetrating traumatic brain injury in adult Drosophila

2021 ◽  
Author(s):  
Khailee Marischuk ◽  
Kassi Lyn Crocker ◽  
Shawn Ahern-Djmali ◽  
Grace Elisabeth Boekhoff-Falk
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Proliferation ◽  
Innate Immunity ◽  
Brain Injury ◽  
Regenerative Process ◽  
Adverse Outcomes ◽  
Early Event ◽  
Immunity Factor ◽  
Integral Role ◽  
Penetrating Traumatic Brain Injury

We are utilizing an adult penetrating traumatic brain injury (PTBI) model in Drosophila to investigate regenerative mechanisms after damage to the central brain. We focused on cell proliferation as an early event in the regenerative process. To identify candidate pathways that may trigger cell proliferation following PTBI, we utilized RNA-Seq. We find that transcript levels for components of both Toll and Immune Deficiency (Imd) innate immunity pathways are rapidly and highly upregulated post-PTBI. We then tested mutants for the NF-κB transcription factors of the Toll and Imd pathways, Dorsal-related immunity factor (Dif) and Relish (Rel) respectively. We find that loss of either or both Dif and Rel results in loss of cell proliferation after injury. We then tested canonical downstream targets of Drosophila innate immune signaling, the antimicrobial peptides (AMPs), and find that they are not required for cell proliferation following PTBI. This suggests that there are alternative targets of Toll and Imd signaling that trigger cell division after injury. Furthermore, we find that while AMP levels are substantially elevated after PTBI, their levels revert to near baseline within 24 hours. Finally, we identify tissue-specific requirements for Dif and Rel. Taken together, these results indicate that the innate immunity pathways play an integral role in the regenerative response. Innate immunity previously has been implicated as both a potentiator and an inhibitor of regeneration. Our work suggests that modulation of innate immunity may be essential to prevent adverse outcomes. Thus, this work is likely to inform future experiments to dissect regenerative mechanisms in higher organisms.

Severe Traumatic Brain Injury

2018 ◽  
Author(s):  
Ryan Martin ◽  
Lara Zimmermann ◽  
Kee D. Kim ◽  
Marike Zwienenberg ◽  
Kiarash Shahlaie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Severe Traumatic Brain Injury ◽  
Neurocritical Care ◽  
Secondary Brain Injury ◽  
Brain Oxygenation ◽  
Barbiturate Coma ◽  
Blast Traumatic Brain Injury ◽  
Penetrating Traumatic Brain Injury

Traumatic brain injury remains a leading cause of death and disability worldwide. Patients with severe traumatic brain injury are best treated with a multidisciplinary, evidence-based, protocol-directed approach, which has been shown to decrease mortality and improve functional outcomes. Therapy is directed at the prevention of secondary brain injury through optimizing cerebral blood flow and the delivery of metabolic fuel (ie, oxygen and glucose). This is accomplished through the measurement and treatment of elevated intracranial pressure (ICP), the strict avoidance of hypotension and hypoxemia, and in some instances, surgical management. The treatment of elevated ICP is approached in a protocolized, tiered manner, with escalation of care occurring in the setting of refractory intracranial hypertension, culminating in either decompressive surgery or barbiturate coma. With such an approach, the rates of mortality secondary to traumatic brain injury are declining despite an increasing incidence of traumatic brain injury. This review contains 3 figures, 5 tables and 69 reference Key Words: blast traumatic brain injury, brain oxygenation, cerebral perfusion pressure, decompressive craniectomy, hyperosmolar therapy, intracranial pressure, neurocritical care, penetrating traumatic brain injury, severe traumatic brain injury

Characterization of a Novel Rat Model of Penetrating Traumatic Brain Injury

2012 ◽  
Vol 29 (6) ◽  
pp. 1219-1232 ◽  
Author(s):  
Stefan Plantman ◽  
Kian Chye Ng ◽  
Jia Lu ◽  
Johan Davidsson ◽  
Mårten Risling
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Model ◽  
Penetrating Traumatic Brain Injury

Cell Proliferation in the Brains of Adult Rats Exposed to Traumatic Brain Injury

2013 ◽  
pp. 27-38
Author(s):  
Sandra A. Acosta ◽  
Naoki Tajiri ◽  
Paula C. Bickford ◽  
Cesar V. Borlongan
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Proliferation ◽  
Brain Injury ◽  
Adult Rats

scholarly journals Prognostic performance of computerized tomography scoring systems in civilian penetrating traumatic brain injury: an observational study

2019 ◽  
Vol 161 (12) ◽  
pp. 2467-2478 ◽  
Author(s):  
Matias Lindfors ◽  
Caroline Lindblad ◽  
David W. Nelson ◽  
Bo-Michael Bellander ◽  
Jari Siironen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Computerized Tomography ◽  
Outcome Prediction ◽  
Unfavorable Outcome ◽  
Receiver Operating Curve ◽  
Excellent Performance ◽  
Head Ct ◽  
Severity Scores ◽  
Penetrating Traumatic Brain Injury

Abstract Background The prognosis of penetrating traumatic brain injury (pTBI) is poor yet highly variable. Current computerized tomography (CT) severity scores are commonly not used for pTBI prognostication but may provide important clinical information in these cohorts. Methods All consecutive pTBI patients from two large neurotrauma databases (Helsinki 1999–2015, Stockholm 2005–2014) were included. Outcome measures were 6-month mortality and unfavorable outcome (Glasgow Outcome Scale 1–3). Admission head CT scans were assessed according to the following: Marshall CT classification, Rotterdam CT score, Stockholm CT score, and Helsinki CT score. The discrimination (area under the receiver operating curve, AUC) and explanatory variance (pseudo-R2) of the CT scores were assessed individually and in addition to a base model including age, motor response, and pupil responsiveness. Results Altogether, 75 patients were included. Overall 6-month mortality and unfavorable outcome were 45% and 61% for all patients, and 31% and 51% for actively treated patients. The CT scores’ AUCs and pseudo-R2s varied between 0.77–0.90 and 0.35–0.60 for mortality prediction and between 0.85–0.89 and 0.50–0.57 for unfavorable outcome prediction. The base model showed excellent performance for mortality (AUC 0.94, pseudo-R2 0.71) and unfavorable outcome (AUC 0.89, pseudo-R2 0.53) prediction. None of the CT scores increased the base model’s AUC (p > 0.05) yet increased its pseudo-R2 (0.09–0.15) for unfavorable outcome prediction. Conclusion Existing head CT scores demonstrate good-to-excellent performance in 6-month outcome prediction in pTBI patients. However, they do not add independent information to known outcome predictors, indicating that a unique score capturing the intracranial severity in pTBI may be warranted.

Drug Repurposing in Neurological Disorders: Implications for Neurotherapy in Traumatic Brain Injury

2020 ◽  
pp. 107385842096107
Author(s):  
Zaynab Shakkour ◽  
Karl John Habashy ◽  
Moussa Berro ◽  
Samira Takkoush ◽  
Samar Abdelhady ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Drug Administration ◽  
Neurological Disorders ◽  
De Novo ◽  
Food And Drug Administration ◽  
Drug Repurposing ◽  
Adverse Outcomes ◽  
Minimal Risk ◽  
Wide Range

Traumatic brain injury (TBI) remains a significant leading cause of death and disability among adults and children globally. To date, there are no Food and Drug Administration–approved drugs that can substantially attenuate the sequelae of TBI. The innumerable challenges faced by the conventional de novo discovery of new pharmacological agents led to the emergence of alternative paradigm, which is drug repurposing. Repurposing of existing drugs with well-characterized mechanisms of action and human safety profiles is believed to be a promising strategy for novel drug use. Compared to the conventional discovery pathways, drug repurposing is less costly, relatively rapid, and poses minimal risk of the adverse outcomes to study on participants. In recent years, drug repurposing has covered a wide range of neurodegenerative diseases and neurological disorders including brain injury. This review highlights the advances in drug repurposing and presents some of the promising candidate drugs for potential TBI treatment along with their possible mechanisms of neuroprotection. Edaravone, glyburide, ceftriaxone, levetiracetam, and progesterone have been selected due to their potential role as putative TBI neurotherapeutic agents. These drugs are Food and Drug Administration–approved for purposes other than brain injuries; however, preclinical and clinical studies have shown their efficacy in ameliorating the various detrimental outcomes of TBI.

scholarly journals Adenosine kinase inhibition promotes proliferation of neural stem cells after traumatic brain injury

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Hoda M Gebril ◽  
Rizelle Mae Rose ◽  
Raey Gesese ◽  
Martine P Emond ◽  
Yuqing Huo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Proliferation ◽  
Stem Cell ◽  
Brain Injury ◽  
Neural Stem Cell ◽  
Adenosine Kinase ◽  
Health Concern ◽  
Stem Cell Proliferation ◽  
Neural Stem Cell Proliferation ◽  
The Brain

Abstract Traumatic brain injury (TBI) is a major public health concern and remains a leading cause of disability and socio-economic burden. To date, there is no proven therapy that promotes brain repair following an injury to the brain. In this study, we explored the role of an isoform of adenosine kinase expressed in the cell nucleus (ADK-L) as a potential regulator of neural stem cell proliferation in the brain. The rationale for this hypothesis is based on coordinated expression changes of ADK-L during foetal and postnatal murine and human brain development indicating a role in the regulation of cell proliferation and plasticity in the brain. We first tested whether the genetic disruption of ADK-L would increase neural stem cell proliferation after TBI. Three days after TBI, modelled by a controlled cortical impact, transgenic mice, which lack ADK-L (ADKΔneuron) in the dentate gyrus (DG) showed a significant increase in neural stem cell proliferation as evidenced by significant increases in doublecortin and Ki67-positive cells, whereas animals with transgenic overexpression of ADK-L in dorsal forebrain neurons (ADK-Ltg) showed an opposite effect of attenuated neural stem cell proliferation. Next, we translated those findings into a pharmacological approach to augment neural stem cell proliferation in the injured brain. Wild-type C57BL/6 mice were treated with the small molecule adenosine kinase inhibitor 5-iodotubercidin for 3 days after the induction of TBI. We demonstrate significantly enhanced neural stem cell proliferation in the DG of 5-iodotubercidin-treated mice compared to vehicle-treated injured animals. To rule out the possibility that blockade of ADK-L has any effects in non-injured animals, we quantified baseline neural stem cell proliferation in ADKΔneuron mice, which was not altered, whereas baseline neural stem cell proliferation in ADK-Ltg mice was enhanced. Together these findings demonstrate a novel function of ADK-L involved in the regulation of neural stem cell proliferation after TBI.

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